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Sotorasib plus Panitumumab in Refractory Colorectal Cancer with Mutated KRAS G12C
Marwan G Fakih1, Lisa Salvatore1, Taito Esaki1
1From Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte (M.G.F.), and Amgen, Thousand Oaks (E.C., J.C., Y.S., Q.T.) - both in California; Oncologia Medica, Università Cattolica del Sacro Cuore, and Oncologia Medica, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome (L.S.), the Oncology Department, Fondazione Poliambulanza Istituto Ospedaliero, Brescia (F.M.), the Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa (C.C.), and the Medical Oncology Department, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale dei Tumori, Milan (F.P.) - all in Italy; the Department of Gastrointestinal and Medical Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka (T.E.), and the Experimental Therapeutics and GI Oncology Department, National Cancer Center Hospital East, Kashiwa (Y.K.) - both in Japan; the Medicine Department of Hematology, Oncology, and Tumor Immunology, Charité-Universitätsmedizin Berlin, Berlin (D.P.M.); the Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau, Barcelona (D.P.L.-B.); Université Paris Cité, Site de Recherche Intégrée sur le Cancer, Cancer Research for Personalized Medicine Comprehensive Cancer Center, Department of Gastroenterology and Digestive Oncology, Hôpital Européen Georges-Pompidou, Paris (J.T.); the Department of Biological Chemistry, National and Kapodistrian University of Athens-School of Medicine, Athens (M.V.K.); Gastrointestinal Oncology Department and Translational Medicine Laboratory, Instituto Nacional de Cancerologia, Mexico City (E.R.-G.); the Oncology Department, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea (T.W.K.); the Medicine Department, Royal Marsden Hospital, London (D.C.); and the Department of Oncology, National Taiwan University Hospital, and the Graduate Institute of Oncology, National Taiwan University College of Medicine - both in Taipei (K.H.Y.).
Combining sotorasib, a KRAS G12C inhibitor, with panitumumab improved progression-free survival in patients with metastatic colorectal cancer. This combination therapy demonstrated superior efficacy compared to standard care, with manageable side effects.
Area of Science:
- Oncology
- Molecular targeted therapy
- Gastrointestinal cancer research
Background:
- KRAS G12C mutations are present in 3-4% of metastatic colorectal cancer (mCRC) cases.
- KRAS G12C inhibitors alone show limited efficacy in mCRC.
- Combination therapy with KRAS G12C and EGFR inhibitors may enhance treatment outcomes.
Purpose of the Study:
- To evaluate the efficacy of combining sotorasib (a KRAS G12C inhibitor) with panitumumab (an EGFR inhibitor) in patients with chemorefractory metastatic colorectal cancer.
- To compare the combination therapy against standard care in a Phase 3 clinical trial.
- To assess progression-free survival (PFS), overall survival (OS), and objective response rate (ORR).
Main Methods:
- Phase 3, multicenter, open-label, randomized trial involving patients with chemorefractory mCRC and KRAS G12C mutation.
- Patients received either 960 mg or 240 mg sotorasib plus panitumumab, or investigator's choice of trifluridine-tipiracil/regorafenib (standard care).
- Primary endpoint was PFS assessed by blinded independent central review; secondary endpoints included OS and ORR.
Main Results:
- Median PFS was significantly longer with sotorasib-panitumumab (5.6 months for 960mg; 3.9 months for 240mg) versus standard care (2.2 months).
- Hazard ratios for disease progression or death were 0.49 (960mg) and 0.58 (240mg) compared to standard care (P<0.05).
- Objective response rates were 26.4% (960mg) and 5.7% (240mg) for sotorasib-panitumumab arms, versus 0% for standard care.
Conclusions:
- Combination of sotorasib and panitumumab significantly improved PFS in patients with chemorefractory metastatic colorectal cancer.
- The observed toxic effects were consistent with monotherapy, leading to minimal treatment discontinuations.
- This combination represents a promising therapeutic strategy for this patient population.
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